The blood-brain barrier (BBB), a protective endothelial tissue surrounding the CNS, is a major impediment to the systemic delivery of high molecular weight therapeutic and diagnostic agents (e.g., antibodies) to the CNS. The present invention represents an advance in macromolecular therapeutic compositions capable of crossing the BBB into the CNS and in the use of such compositions in diagnostic and therapeutic applications (e.g., treatment of Alzheimer's disease).